Diethyl Ether → 4-Chloro-2-hydroxybenzaldehyde

Modification of a procedure described by G. Casiraghi et al., (J. Chem. Soc., Perkin Transac. I., 1978, 318), was utilized in the preparation of substituted salicylaldehydes. To a mixture of 26 g of 3-chlorophenol dissolved in 200 mL, of toluene at 10° C. was added dropwise 100 mL, of a 2M solution of ethylmagnesium chloride in diethyl ether. The ether was distilled off and the reaction mixture was cooled to room temperature and 26.0 g of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) was added followed by 15.0 g of paraformaldehyde. The reaction mixture was heated at 70° C. for 18 h, cooled to 10° C. and a solution of 20 mL of concentrated HCl in 100 g of ice was added followed by 200 mL of hexane. The organic phase was separated and washed twice with 100 mL of water, once with 100 mL of brine, dried over anhydrous MgSO4, filtered and concentrated under vacuum to afford a viscous oil. This was taken up in 150 mL of ethanol and a solution of 15.0 g of copper (II) acetate dissolved in 150 mL of H2O was added dropwise. The resulting precipitate was filtered, washed with water and then with ether and added to a solution of 200 mL of ether and 20 mL of concentrated H2SO4 in 100 g of ice. The mixture was stirred until ail solids were dissolved, 100 mL of hexane was added, and the organics were washed with 100 mL of H2O, then 100 mL of brine, dried over anhydrous MgSO4, filtered and concentrated under vacuum to afford 15.0 g of a yellow solid, mp 47°-48° C. 1H NMR (CDCl3) δ6.98 (d, 1H), 7.01 (s, 1H), 7.50 (d, 1H), 9.85 (s, 1H), 11.18 (s, 1H). IR (Nujol) 3300-2800, 1670 cm-1.

1. additionwas added dropwise 100 mL
2. distillationThe ether was distilled off
3. addition26.0 g of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) was added
4. temperatureThe reaction mixture was heated at 70° C. for 18 h
5. temperaturecooled to 10° C.
6. additiona solution of 20 mL of concentrated HCl in 100 g of ice was added
7. customThe organic phase was separated
8. washwashed twice with 100 mL of water, once with 100 mL of brine
9. dry with materialdried over anhydrous MgSO4
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customto afford a viscous oil
13. additionwas added dropwise
14. filtrationThe resulting precipitate was filtered
15. washwashed with water
16. additionwith ether and added to a solution of 200 mL of ether and 20 mL of concentrated H2SO4 in 100 g of ice
17. dissolutionwere dissolved
18. addition100 mL of hexane was added
19. washthe organics were washed with 100 mL of H2O
20. dry with material100 mL of brine, dried over anhydrous MgSO4
21. filtrationfiltered
22. concentrationconcentrated under vacuum

ORD record

ord-9a7d764d565e4ab3b0b40fe6aa1efc3d

Source dataset

uspto-grants-1995_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05474998